RESUMO
BACKGROUND: PRDM12 polyalanine tract expansions cause two different disorders: midfacial toddler excoriation syndrome (MiTES; itch with normal pain sensation associated with 18 homozygous alanines (18A); and congenital insensitivity to pain (CIP) with normal itch associated with 19 homozygous alanines (19A). Knowledge of the phenotype, genotype and disease mechanism of MiTES is incomplete. Why 18A vs. 19A PRDM12 can cause almost opposite phenotypes is unknown; no other polyalanine or polyglutamine tract expansion disease causes two such disparate phenotypes. OBJECTIVES: To assess the genotype and phenotype of nine new, nine atypical and six previously reported patients diagnosed with MiTES. METHODS: Using cell lines with homozygous PR domain zinc finger protein 12 (PRDM12) containing 12 alanines (12A; normal), 18A (MiTES) and 19A (CIP), we examined PRDM12 aggregation and subcellular localization by image-separation confocal microscopy and subcellular fractionation Western blotting. RESULTS: MiTES presents in the first year of life; in all cases the condition regresses over the first decade, leaving scarring. The MiTES phenotype is highly distinctive. Features overlapping with PRDM12 CIP are rarely found. The genotype-phenotype study of the PRDM12 polyalanine tract shows that having 7-15 alanines is normal; 16-18 alanines is associated with MiTES; 19 alanines leads to CIP; and no clinically atypical cases of MiTES had a polyalanine tract expansion. PRDM12 aggregation and subcellular localization differed significantly between 18A and normal 12A cell lines and between 18A and 19A cell lines. MiTES is a new protein-aggregation disease. CONCLUSIONS: We provide diagnostic criteria for MiTES and improved longitudinal data. MiTES and CIP are distinct phenotypes, despite their genotypes varying by a single alanine in the PRDM12 polyalanine tract. We found clear distinctions between the cellular phenotypes of normal, MiTES and CIP cells. We hypothesize that the developmental environment of the trigeminal ganglion is unique and critically sensitive to pre- and postnatal levels of PRDM12.
Midfacial toddler excoriation syndrome (MiTES) causes facial itching and scratching in babies during their first year of life. MiTES tends to improve over the time period of approximately 10â years, but it can leave scars. Congenital insensitivity to pain (CIP) is a condition where a person cannot feel pain and is present from birth. This study looked at two conditions: MiTES and CIP. We specifically investigated changes in a gene called PRDM12, focusing on a part of the gene called the polyalanine tract a sequence of many alanines (alanine is a type of amino acid). We discovered that the normal range for this sequence is between 7 and 15 alanines. If there are 16 to 18 alanines, it is associated with MiTES and causes the PRDM12 protein to clump together inside the cell. However, if there are 19 alanines, it leads to CIP, and the PRDM12 protein clumps together and moves to the cytoplasm, where it should not be. We found new evidence to suggest that MiTES is a disease where proteins clump together. Overall, our study findings show that despite there only being a small change in the same gene, MiTES and CIP are very different conditions.
Assuntos
Fenótipo , Humanos , Masculino , Feminino , Pré-Escolar , Lactente , Genótipo , Criança , Síndrome , Proteínas do Tecido Nervoso/genética , Neuropatias Hereditárias Sensoriais e Autônomas/genética , Neuropatias Hereditárias Sensoriais e Autônomas/diagnóstico , Proteínas de TransporteRESUMO
We aimed to investigate roles of dermatoscopy in skin infections, with Part 1 of our report covering viral and bacterial infections. A case-control study was conducted on the medical records of all patients with skin infections who had had dermatoscopy performed over a period of 3 months. Our control participants were all patients with skin infections in two 3-month periods, and sex-pair-matched patients with the same infections, who had not undergone dermatoscopy. Records of 523 study subjects were analyzed. Our first new finding was that dermatoscopy brought forward the diagnosis of herpes zoster by 1.62 days (95% confidence interval [CI] 0.29 to 0.34 days; z-score -2.18). Second, dermatoscopy facilitated the diagnosis of genital (P<.01) and small extragenital risk ratio [RR] 1.28, 95% CI 1.03 to 1.59) viral warts. Third, patients with genital herpes and/or genital warts and/or genital molluscum contagiosum diagnosed by clinical examination and dermatoscopy were significantly more willing to pay US$300 to investigate for other sexually transmitted infections (STIs) (RR 2.52, 95% CI 1.32 to 3.18), and bring partners for investigation (RR 1.32, 95% CI 1.12 to 1.55), compared to patients diagnosed by clinical examination alone. We performed dermatoscope-guided laser ablation on viral warts, and dermatoscopy-guided excisional biopsy to confirm molluscum contagiosum. We conclude that dermatoscopy contributes to the diagnosis of some viral and bacterial infections. In addition, it may modify the help-seeking behaviour of patients with STIs.
Assuntos
Dermoscopia , Atenção Primária à Saúde , Dermatopatias Infecciosas/diagnóstico , Estudos de Casos e Controles , Humanos , Dermatopatias Infecciosas/microbiologia , Dermatopatias Infecciosas/virologiaRESUMO
Eruptive pseudoangiomatosis is a distinct exanthem thought to be caused by viruses. The usual rash configu-ration is erythematous papules and macules. An association with echovirus infection has been reported. We present here one adult and one child with this exanthem, supported by clinical, histopathological, and immunohistochemical findings. Both patients presented with prodromal symptoms, widespread angioma-like macules in annular configuration, blanchable telangiectasia, followed by spontaneous remission in 6-8 weeks. Lesional histopathology of the adult patient revealed dilated dermal blood vessels and lymphohistiocytic infiltrates predominated by CD4+ lymphocytes with a 5:1 ratio of CD4:CD8 lymphocytes. No B cells or CD56+ natural killer cells were found. Serology of both patients revealed evidence of active infections by adenoviruses, and a range of other viruses were excluded. We believe that these 2 patients manifested annular eruptive pseudoangio-matosis, a novel variant of the rash with a probable adenovirus association that has not yet been reported.
Assuntos
Infecções por Adenoviridae/virologia , Adenoviridae/patogenicidade , Angiomatose/virologia , Exantema/virologia , Pele/virologia , Adenoviridae/imunologia , Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/imunologia , Angiomatose/diagnóstico , Angiomatose/imunologia , Biópsia , Pré-Escolar , Exantema/diagnóstico , Exantema/imunologia , Humanos , Imuno-Histoquímica , Masculino , Remissão Espontânea , Pele/imunologia , Pele/patologia , Fatores de Tempo , Adulto JovemRESUMO
We recently reported a wave of nine children with a novel paraviral exanthem, which we have termed eruptive hypomelanosis. We subsequently witnessed a second wave of children with this exanthem and present a patient here to alert clinicians.
Assuntos
Exantema/diagnóstico , Exantema/virologia , Hipopigmentação/diagnóstico , Hipopigmentação/virologia , Diagnóstico Diferencial , Humanos , Lactente , MasculinoRESUMO
OBJECTIVES: To investigate whether Gianotti-Crosti syndrome (GCS) in children is associated with atopy. METHODS: The setting was two outpatient clinic. Diagnoses of asthma and atopic dermatitis (AD) were made according to internationally accepted diagnostic criteria. Allergic rhinitis, atopic urticaria, and allergic conjunctivitis were diagnosed clinically. Participants were children with GCS diagnosed over the previous 5 years. For any child with GCS, we extracted the record of the subsequent age and sex pair-matched child seen for problems unrelated to the skin as controls. RESULTS: We retrieved the records of 37 pairs of study and control subjects; 28 (76%) children with GCS and 9 (24%) controls had AD (risk ratio [RR] = 3.11[95% confidence interval {CI} 1.73, 5.73]), 31 (84%) children with GCS and 19 (51%) controls had at least one atopic condition (RR = 1.63 [95% CI 1.13, 2.18]) and 11 (30%) children with GCS and 2 (5%) controls had at least three atopic conditions (RR = 5.50 [95% CI 1.29, 35.35]). CONCLUSION: GCS is significantly associated with AD and the presence of atopic conditions.
Assuntos
Acrodermatite/epidemiologia , Acrodermatite/imunologia , Hipersensibilidade/epidemiologia , Hipersensibilidade/imunologia , Distribuição por Idade , Instituições de Assistência Ambulatorial , Asma/epidemiologia , Asma/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Comorbidade , Intervalos de Confiança , Dermatite Atópica/epidemiologia , Dermatite Atópica/imunologia , Feminino , Hospitais de Ensino , Humanos , Lactente , Masculino , Prevalência , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Distribuição por SexoRESUMO
Woronoff ring has been mostly discussed as a phenomenon in psoriasis, especially during therapy. It has also been reported in a few other conditions unrelated to psoriasis; however, the association of Woronoff ring has not been reported in immunocompetent, healthy, and untreated patients with molluscum contagiosum who have no apparent systemic illness. The authors report a case series of Woronoff ring seen in untreated immunocompetent patients with molluscum contagiosum involving different age groups.
Assuntos
Imunocompetência , Molusco Contagioso/patologia , Humanos , Psoríase/patologiaAssuntos
Hanseníase Dimorfa/diagnóstico , Mycobacterium leprae/isolamento & purificação , Doenças do Tecido Conjuntivo Indiferenciado/diagnóstico , Anticorpos Antibacterianos/análise , Diagnóstico Diferencial , Humanos , Hanseníase Dimorfa/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Doenças NegligenciadasAssuntos
Candidíase/diagnóstico , Candidíase/terapia , Crioterapia/métodos , Dermatoses do Pé/terapia , Nitrogênio/uso terapêutico , Adulto , Doença Crônica , Estudos de Coortes , Feminino , Seguimentos , Dermatoses do Pé/microbiologia , Humanos , Índia , Masculino , Projetos Piloto , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Dedos do Pé , Resultado do TratamentoAssuntos
Túnica Conjuntiva/patologia , Técnicas de Diagnóstico Oftalmológico/instrumentação , Deficiência de Vitamina A/diagnóstico , Xeroftalmia/diagnóstico , Adolescente , Diagnóstico Diferencial , Desenho de Equipamento , Feminino , Humanos , Deficiência de Vitamina A/complicações , Xeroftalmia/etiologiaAssuntos
Angioedema/diagnóstico , Países em Desenvolvimento , Dermatoses Faciais/diagnóstico , Hanseníase Multibacilar/diagnóstico , Sinusite/diagnóstico , Adolescente , Angioedema/tratamento farmacológico , Angioedema/patologia , Biópsia , Doença Crônica , Clofazimina/uso terapêutico , Dapsona/uso terapêutico , Diagnóstico Diferencial , Quimioterapia Combinada , Dermatoses Faciais/tratamento farmacológico , Dermatoses Faciais/patologia , Seguimentos , Humanos , Índia , Hanseníase Multibacilar/tratamento farmacológico , Hanseníase Multibacilar/patologia , Masculino , Rifampina/uso terapêutico , Sinusite/tratamento farmacológico , Sinusite/patologia , Pele/patologiaRESUMO
BACKGROUND: Although well known in clinical practice, research in lichen planus pigmentosus and related dermal pigmentary diseases is restricted due to lack of consensus on nomenclature and disease definition. AIMS AND OBJECTIVES: Delphi exercise to define and categorise acquired dermal pigmentary diseases. METHODS: Core areas were identified including disease definition, etiopathogenesis, risk factors, clinical features, diagnostic methods, treatment modalities and outcome measures. The Delphi exercise was conducted in three rounds. RESULTS: Sixteen researchers representing 12 different universities across India and Australia agreed to be part of this Delphi exercise. At the end of three rounds, a consensus of >80% was reached on usage of the umbrella term 'acquired dermal macular hyperpigmentation'. It was agreed that there were minimal differences, if any, among the disorders previously defined as ashy dermatosis, erythema dyschromicum perstans, Riehl's melanosis and pigmented contact dermatitis. It was also agreed that lichen planus pigmentosus, erythema dyschromicum perstans and ashy dermatosis did not differ significantly apart from the sites of involvement, as historically described in the literature. Exposure to hair colours, sunlight and cosmetics was associated with these disorders in a significant proportion of patients. Participants agreed that both histopathology and dermatoscopy could diagnose dermal pigmentation characteristic of acquired dermal macular hyperpigmentation but could not differentiate the individual entities of ashy dermatosis, erythema dyschromicum perstans, Riehl's melanosis, lichen planus pigmentosus and pigmented contact dermatitis. LIMITATIONS: A wider consensus involving representatives from East Asian, European and Latin American countries is required. CONCLUSION: Acquired dermal macular hyperpigmentation could be an appropriate conglomerate terminology for acquired dermatoses characterised by idiopathic or multifactorial non-inflammatory macular dermal hyperpigmentation.